1. Field of the Invention
One or more embodiments of the invention relate generally to a process for deriving pomegranate extracts and methods of using thereof, and more specifically but not by way of limitation to methods of using pomegranate extracts to treat diabetes related complications and atherosclerosis in humans.
2. Description of the Related Art
Diabetes mellitus is associated with increased oxidative stress and atherosclerosis development. Diabetes is increasing worldwide, resulting from the interaction of obesity, inflammation and hyperglycemia. Both type I and type II diabetes are powerful and independent risk factors for coronary artery disease, stroke and peripheral arterial disease, and atherosclerosis accounts for 80% of all deaths among diabetic patients. Prolonged exposure to hyperglycemia is now recognized as a major risk factor in the pathogenesis of atherosclerosis in diabetes. Animal and human studies elucidated three major mechanisms for the pathological alterations observed in diabetic vasculature, i.e. non-enzymatic glycosylation of proteins and lipids which can interfere with their normal function, cellular protein kinase C (PKC) activation and oxidative stress.
Diabetic patients may be highly prone to oxidative stress because hyperglycemia depletes natural anti-oxidants and facilitates the production of free radicals. Thus, anti-oxidants treatment in diabetes could be beneficial. Indeed, it was shown that alpha-tocopherol supplementation to diabetic patients significantly reduced serum oxidative stress. Furthermore, tea catechins were able to protect diabetic erythrocytes from tert-butyl hydroperoxide-induced oxidative stress.
Macrophages play a major role in the early stages of atherogenesis. Recent studies that were performed in control subjects or in diabetic patients' monocytes-macrophages demonstrated that high glucose levels can lead to macrophage foam cell formation by several mechanisms including: increased cholesterol synthesis, altered expression and secretion of lipoprotein lipase, monocytes PKC activation and up-regulation of an oxidized LDL (LOX-1) receptor, or scavenger receptors. Increased oxidative stress and increased uptake of Ox-LDL also in peritoneal macrophages from streptozotocin-induced diabetic mice, as well as in vitro, is thought to be present in cells incubated with high glucose levels.
A balanced diet, with careful attention given to the carbohydrates consumed, plays a prominent role in improving glycemia and other diabetic outcomes. As recently as 2004, the carbohydrate recommendations as stated by the American Diabetes Association (ADA) in their clinical practice recommendations for that year focused on the absolute importance of the total amount of carbohydrate consumption per meal or snack and attributed little importance to its food source. However, since evidence continues to accumulate on the efficacy of the type of carbohydrate consumed in promoting normal or improved glycemia in diabetes patients, the 2005 ADA recommendations now indicate that “use of the glycemic index/glycemic load can provide an additional benefit over that observed when total carbohydrate is considered alone”. For this reason, diabetic patients usually avoid sugar-containing juices, such as grape juice, which can worsen their diabetic conditions and atherosclerotic complications.
Pomegranate juice (PJ) possesses impressive antioxidative properties due to its polyphenolics, tannins, and proanthocyanins. Consumption of PJ by humans for a period of 1 year significantly reduced the oxidation of both LDL and HDL. Furthermore, in patients with carotid artery stenosis that consumed PJ for 3 years, we demonstrated reduced oxidative stress in their blood, and a decreased atherosclerotic lesion size. PJ, which contains about 10% sugars, have similar glycemic index to that of other fruit juices such as grape juice.
A need exists, however, for a composition that has a palatable taste but still provides beneficial effects when manifested in diabetic patients with atherosclerotic complications.